Plasticity of the brain that allows its function to change adaptively in response to experience is one of the most important properties of the central nervous system. Plastic changes, occurring on synapses, are probably the most important ones because they may alter communication between neurons. Hippocampus proper and the dentate fascia are regions which show a number of age related changes. A loss of perikarya and synaptic contaats, regression of dendritic spines and dendrites were described to varying degrees in both regions. Since also a dendritic growth has been observed, which implies synapse sprouting or relocation, the ultrastructure of the neuropile will be studied in both regions. There are indications that a loss or alteration of synaptic plasticity in the hippocampus may account for a number of problems in memory and performance associated with senescence. In view of this, the proposed experiments are attempting to identify the possible cytological and cytochemical substrates which could explain changes in plastic reactions of an aging brain. Various forms of synaptic plascticity suggest that they may have a common denominator which could be linked to actin. This contractile protein is known to be present in neurons similarly to other nonmuscle cells. Actin filaments in neurons may have a dual role: as support providing elements and as a substrate for plastic reactions. With this assumption in mind, we propose to investigate the organization of actin filaments in dendritic spines, dendrites and axon terminals in the hippocampal formation of senescent rats. Of special interest will be the relation of actin filaments to: a) the plasma membrane, the pre-and postsynaptic membrane specializations and to the postsynaptic density; b) other cytoplasmic organelles, notably to the spine apparatus, smooth endoplasmic reticulum, microtubulues and synaptic vesicles. Actin microfilaments will be identified using actin's affinity to the S-1 subfragment of myosin. The spatial relation of microfilaments will be studied in stereomicrographs taken with the high voltage electron microscope. Because properties of actin filaments are critically affected by free cytoplasmic Ca++, the intracellular distribution of this ion will be studied using cytochemical calcium precipitation techniques either in freeze-substituted or aldehyde fixed tissue. The distribution of this cation will be correlated with the fine structure of hippocampal neurons under different conditions of excitation in aged rats and controls.